| Flow-dependent channel formation in clots by an erythrocyte-bound fibrinolytic agent. | |
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MedLine Citation:
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PMID: 21389322 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Studies in animal models have shown that plasminogen activators bound to erythrocytes (RBC-PA) have an extended lifetime in the circulation and are safer than free PAs. RBC-PAs incorporate into nascent thrombi, which are focally lysed from within, an attractive thromboprophylactic option. In static systems, RBC-PAs cleave surrounding fibrin fibers, forming pores larger than the cells themselves, and move around the pore edges, enlarging them until eventual clot dissolution. We hypothesized that under flow in blood vessels, RBC-PAs form functional patent channels before clot dissolution. Here we used perfusion chambers to study clot lysis by RBC-PAs under static versus arterial and venous flow conditions. We found that flow decelerates bulk clot lysis but quickly generates patent channels filled with passing RBCs, via pore enlargement and merging in the direction of flow. Formation of such channels by RBC-PAs may help rescue ischemic tissue before bulk dissolution of potentially occlusive clots. |
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Authors:
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Kathryn C Gersh; Sergei Zaitsev; Douglas B Cines; Vladimir Muzykantov; John W Weisel |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural Date: 2011-03-09 |
Journal Detail:
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Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-06 Completed Date: 2011-07-05 Revised Date: 2012-05-08 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 4964-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Cell & Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Coagulation / drug effects*, physiology Erythrocytes / drug effects, physiology Fibrinolytic Agents / pharmacology* Hemorheology Humans Mice Microscopy, Confocal Models, Biological Plasminogen Activators / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HD-057355/HD/NICHD NIH HHS; HL-076406/HL/NHLBI NIH HHS; HL-077760/HL/NHLBI NIH HHS; HL090774/HL/NHLBI NIH HHS; HL30954/HL/NHLBI NIH HHS; R01 HL090774-04/HL/NHLBI NIH HHS; R01-HL090697/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fibrinolytic Agents; EC 3.4.21.-/Plasminogen Activators |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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